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- Title
Dysregulation of lncRNA MALAT1 Contributes to Lung Cancer in African Americans by Modulating the Tumor Immune Microenvironment.
- Authors
Li, Jin; Dhilipkannah, Pushpa; Holden, Van K.; Sachdeva, Ashutosh; Todd, Nevins W.; Jiang, Feng
- Abstract
Simple Summary: African American (AA) populations experience higher lung cancer incidence and mortality rates. We explore the role of long non-coding RNAs (lncRNAs) in these disparities and their clinical potential. AA lung cancer patients show elevated MALAT1 and PVT1 levels compared to cancer-free smokers. Using these lncRNAs as plasma biomarkers, combined with smoking history, achieved 81% diagnostic accuracy in AA patients. MALAT1 upregulation correlates with increased tumor-associated macrophages and tumor growth. MALAT1 interacts with miR-206, affecting MCP-1 expression and macrophage activity, promoting tumorigenesis. Targeting MALAT1 reduces tumor sizes in animal models. Dysregulated MALAT1 contributes to lung cancer disparities in AAs, suggesting novel diagnostic and therapeutic targets. African American (AA) populations present with notably higher incidence and mortality rates from lung cancer in comparison to other racial groups. Here, we elucidated the contribution of long non-coding RNAs (lncRNAs) in the racial disparities and their potential clinical applications in both diagnosis and therapeutic strategies. AA patients had elevated plasma levels of MALAT1 and PVT1 compared with cancer-free smokers. Incorporating these lncRNAs as plasma biomarkers, along with smoking history, achieved 81% accuracy in diagnosis of lung cancer in AA patients. We observed a rise in MALAT1 expression, correlating with increased levels of monocyte chemoattractant protein-1 (MCP-1) and CD68, CD163, CD206, indicative of tumor-associated macrophages in lung tumors of AA patients. Forced MALAT1 expression led to enhanced growth and invasiveness of lung cancer cells, both in vitro and in vivo, accompanied by elevated levels of MCP-1, CD68, CD163, CD206, and KI67. Mechanistically, MALAT1 acted as a competing endogenous RNA to directly interact with miR-206, subsequently affecting MCP-1 expression and macrophage activity, and enhanced the tumorigenesis. Targeting MALAT1 significantly reduced tumor sizes in animal models. Therefore, dysregulated MALAT1 contributes to lung cancer disparities in AAs by modulating the tumor immune microenvironment through its interaction with miR-206, thereby presenting novel diagnostic and therapeutic targets.
- Subjects
RNA metabolism; AFRICAN Americans; CANCER invasiveness; MACROPHAGES; RESEARCH funding; CELL physiology; TUMOR markers; DESCRIPTIVE statistics; CELL lines; LUNG tumors; GENE expression profiling
- Publication
Cancers, 2024, Vol 16, Issue 10, p1876
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers16101876